The cells lining our blood vessels produce a substance that normally causes arteries to relax. The substance is called endothelium-derived relaxing factor (EDRF). The purpose of this study was to determine the relative importance of EDRF in relaxing blood vessels and preventing blood clot formation in our vessels. The release of EDRF may be impaired in some patients. EDRF release leads to inactivation of platelets. We measure platelet function using impedance aggregometry in 11 normal and 19 patients with atherosclerosis. The measurements were made simultaneously in the effluent and affluent of the right leg at baseline and after 2 minutes stimulation of EDRF release done by intra- arterial infusion of acetylcholine. Blood flow in the arteries was measured by a Doppler flow velocity probe. There was no difference at baseline and platelet function between the vein and the artery in both the normals and the patients with atherosclerosis. Acetylcholine caused a significant inhibition of platelet function. This response was blunted in patients with a diseased endothelium, found in a patient with atherosclerosis.